A model for axon navigation based on glycocodes in the primary olfactory system.

In rodents, primary olfactory sensory neurons reside in the psuedostratified olfactory neuroepithelium lining the caudal nasal cavity. Each neuron expresses a single odorant receptor and all neurons expressing the same receptor are typically located in one of four bands of neuroepithelium lining the nasal cavity (Buck and Axel, 1991; Vassar et al., 1993, 1994). While there are ~1000 different odorant receptor genes, there are probably many more distinct subpopulations of sensory neurons due to regional differences in the nasal cavity of expression of cell surface carbohydrates (Key and Akeson, 1993; Puche and Key, 1996; Dowsing et al., 1997; St John and Key, 2001; Storan et al., 2004) and putative cell adhesion molecules such as OCAM (Yoshihara et al., 1997). The differential expression of odorant receptors does more than just provide a large repertoire of sensory receptors for the detection of odors. These molecules have been shown to play a major axon guidance role (Mombaerts et al., 1996). All primary olfactory neurons expressing the same odorant receptor protein project axons to the olfactory bulb where they converge and typically form two synaptic glomeruli with the dendrites of second-order olfactory neurons and interneurons. While this projection pattern in itself is not unique it is the fact that these glomeruli are positioned in topographically fixed positions in the bulb that creates a complex navigational problem for growth cones. In the retinotecal pathway, retinal neurons project topographically from the retina on to the tectum in a point-to-point map. The maintenance of near-neighbor relations between the sense organ and the target allows the use of complementary gradients of chemorepulsive receptors and ligands to simply determine the topography. This is not the case in the primary olfactory system since the mosaic and stochastic expression of odorant receptors in the olfactory neuroepithelium negates the use of any simple matching gradient of ligand in the bulb. Moreover, it requires that the axons of highly dispersed neurons must sort out and converge on to defined points in space in the bulb at positions which have little spatial correlation to the position of parent neurons in the nasal cavity. Mechanisms are needed to sort about 1000 different subpopulations of axons to enable them to converge and form glomeruli.